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Description / Table of Contents: Abstract. Etomidate is a hypnotic with only minor effects on haemodynamics. Although its rapid elimination kinetics would suggest its use in total intravenous anaesthesia (TIVA) and sedation, its administration in higher doses or for a prolonged period has been discouraged due to its inhibitory effects on corticosteroid synthesis. Newer evidence that the suppression of cortisol synthesis might not be total requires a re-evaluation of this drug as a component of a TIVA technique. The effects of high-dose etomidate with fentanyl on spontaneous and stimulated corticosteroid levels as a measure of the magnitude and duration of adrenocortical suppression, as well as on plasma concentrations of adrenocorticotropic hormone (ACTH) β-endorphin, and catecholamines during cardiac surgery were investigated in a prospective, randomised study and compared to those following the administration of midazolam-fentanyl. Patients and methods. Nineteen patients undergoing myocardial revascularisation were assigned to two groups: group 1: etomidate-fentanyl (n=9) and group 2: midazolam-fentanyl (n=10). Anaesthesia was induced with fentanyl 0.5 mg and either etomidate 0.3 mg/kg or midazolam 0.2 mg/kg. Relaxation was achieved with pancuronium 0.1 mg/kg. Anaesthesia was maintained during extracorporeal circulation (ECC) with an infusion of etomidate (0.36 mg⋅kg−1⋅h−1) or midazolam (0.16 mg⋅kg−1⋅h−1) and fentanyl (10 µg⋅kg−1⋅h−1. Blood samples were drawn before induction, before ECC, and 1, 6, and 20 h after surgery. Cortisol secretion was stimulated with 0.25 mg ACTH1 – 24 IV at 6 and 20 h postoperatively. Results. The total drug doses were etomidate 87±3 mg and midazolam 46±2 mg. Plasma cortisol concentrations decreased in the etomidate group from 20 (10 – 31) to 10 (6 – 31) µg⋅dl−1 (median and range) before ECC, but had returned to baseline at 1 h and were significantly increased at 6 h [29 (15 – 47) µg⋅dl−1] and 20 h [46 (29 – 62) µg⋅dl−1]. There was no difference between the groups except at 20 h, when cortisol levels were higher in the etomidate group. The stimulated cortisol increase was markedly impaired in this group at both measuring points. ACTH and β-endorphin were markedly increased in the etomidate group and ACTH concentrations were eight times greater than the corresponding values in the midazolam group after surgery (ACTH 141 vs. 18 pmol⋅l−1). Plasma catecholamine concentrations increased significantly in both groups. Noradrenaline concentrations were greater in the etomidate group at 6 h after surgery. Two patients in the midazolam group and none in the etomidate group required circulatory support with exogenous catecholamines. Discussion. It is concluded that the stress of cardiac surgery can overcome the block in cortisol synthesis caused by the administration of high-dose etomidate by substantially increasing ACTH secretion. The administration of high-dose etomidate was not associated with cardiovascular instability. The use of etomidate as a component of TIVA can therefore not be ruled out on the grounds of insufficient cortisol secretion.